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Mopping up after messy polymerases and more…
Author(s) -
Hingorani Manju M
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.526.2
Subject(s) - dna mismatch repair , mutagenesis , dna , dna damage , dna replication , dna repair , computational biology , biology , sos response , base pair , function (biology) , polymerase , genetics , dna polymerase , mutation , chemistry , microbiology and biotechnology , gene
The DNA mismatch repair system (MMR) helps maintain the integrity of the genome by locating and correcting base pair mismatches and other replication errors in DNA, and suppressing recombination between non‐identical DNA sequences. Given its critical role in controlling mutagenesis, it is not surprising that defects in MMR protein function underlie an estimated 15 – 25% of a broad spectrum of sporadic cancers as well as a high fraction of the hereditary non‐polyposis colon cancer syndrome. MMR has another important protective function, and that is to mediate cytotoxic effects of DNA damage, e.g., from alkylating agents found in tobacco smoke or chemotherapy. We are interested in understanding the workings of protein components of the MMR system, and to this end we are currently studying MutS protein (from S. cerevisiae and T. aquaticus ), which recognizes defects in DNA and utilizes ATP to signal repair or apoptosis. By measuring kinetic and equilibrium constants that define individual steps in the MutS‐catalyzed reaction, we aim to develop a comprehensive model describing the mechanism of action of this protein, and thus establish a basis for understanding how it detects and mounts selective responses to irregularities such as mismatches or lesions in DNA.